An update on the long-term outcomes of prenatal dexamethasone treatment in congenital adrenal hyperplasia

Abstract

First-trimester prenatal treatment with the glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in girls with CAH, it entails exposure to high doses of GC in foetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow up research is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing, as well as studies assessing dosing effects of DEX may avoid unnecessary treatment and improve treatment safety.

Prenatal diagnosis and in utero treatment of congenital adrenal hyperplasia: An up‐to‐date comprehensive review

“…It is important to highlight that DEX cannot prevent a child from being born with CAH, but it may prevent virilization of the developing female genitalia 4,44 . This timeframe is preferred as we would like to ensure that the fetal labioscrotal folds have yet to close and the female fetuses do not start to develop genitalia that physically fit a male phenotype; initiation following this timeframe may prove to be more ineffective compared to counterparts that did not receive DEX as promptly 45 . DEX dosing is continued throughout the pregnancy until fetal sex is determined to be male or if the fetus is deemed not to have CAH 46 (Figure 2).…”

“…Van't Westeinde et al 45 . described a wide range of fetal effects that DEX therapy can have, from aberrant molecular programming to epigenetics.…”

“…Molecular signaling associated with neurogenesis is thought to be impacted by exogenous steroids, which can lead to potential behavioral and cognitive complications. Genetic modification can be a subsequent complication of steroid use, leading to disarrayed action in organs such as the HPA and the placenta; these changes allow for increased fetal exposure to cortisol 45 . Shinwell et al 56 .…”

“…4,44 This timeframe is preferred as we would like to ensure that the fetal labioscrotal folds have yet to close and the female fetuses do not start to develop genitalia that physically fit a male phenotype; initiation following this timeframe may prove to be more ineffective compared to counterparts that did not receive DEX as promptly. 45 DEX dosing is continued throughout the pregnancy until fetal sex is determined to be male or if the fetus is deemed not to have CAH 46 (Figure 2). The concern arises regarding the continued use of DEX in unaffected females and affected male fetuses, as animal studies suggest that long duration treatment with DEX can potentially lead to adverse effects on the developing fetal brain, highlighting the need to stop the DEX therapy as soon as it is deemed to be clinically unnecessary.…”

“…55 Monkeys were receiving this dosage of DEX were also prone to neurotoxicity, leading to an increased risk of behavioral and emotional issues. 55 Van't Westeinde et al 45 described a wide range of fetal effects that DEX therapy can have, from aberrant molecular programming to epigenetics. Molecular signaling associated with neurogenesis is thought to be impacted by exogenous steroids, which can lead to potential behavioral and cognitive complications.…”